A krypton-fluorine excimer laser at a 248-nm wavelength was used to irradiate normal and severely atherosclerotic segments of human postmortem femoral arteries. Single pulses and multiple pulses required for penetration or perforation of the arterial wall were applied with 16 nsec pulse width and 5 J/cm2/pulse energy fluence. The total fluorescence of irradiated and ablated tissue was analyzed in real-time mode by means of spectroscopy. Each laser pulse produced one spectrum that was characteristic of the composition of the tissue layer, which was ablated. Fluorescence spectroscopy indicated a broad-continuum emission between 300 and 700 nm with peak fluorescence of equal intensity at wavelengths of 370 and 460 nm (ratio, 1.004 +/- 0.087) for normal media layers. Atheromas without calcification (lipid, fibrous, and mixed) were found with spectral maxima at the same wavelengths but with significantly reduced intensity at 460 nm (ratio, 1.765 +/- 0.263; p less than 0.001). In contrast to this broad-continuum fluorescence, calcified plaques displayed multiple-line emission with the most prominent peaks at wavelengths of 397, 442, 450, 461, 528, and 558 nm. These fluorescence criteria identified the histologically classified target tissue precisely. Histological examination of the corresponding arterial layers indicated sharply delineated and circumscribed tissue ablation. These results indicate that simultaneous tissue identification (diagnosis) and ablation (treatment) by excimer laser irradiation is feasible under strict laboratory conditions. We conclude that this principle demonstrates the potential for laser beam control by means of target-specific ablation.